Abnormal tissue oxygenation and cardiovascular changes in endotoxemia

Experimental sepsis induces disturbances in microcirculatory flow and nutri ent exchange that may result in impaired tissue oxygenation. Volume resusci tation is a principal clinical intervention in patients with sepsis. Nitric oxide (NO) has been implicated in the pathophysiology of endotoxemia, but few data exist concerning the effects of either NO synthase inhibition (NOS i) or volume resuscitation on microvascular regulation and tissue oxygenati on. Amperometric measurements were made of skeletal muscle (tissue) oxygen tension (Pt-O2) and its response to changes in fraction of inspired oxygen (FIO2) in rats rendered endotoxemic. Simultaneous measurements were made of systemic hemodynamic indices and arterial blood gas tensions. At normal Pa -O2, Pt-O2 in endotoxemic animals was significantly lower than in control a nimals, with marked attenuation of the response to increasing FIO2. These c hanges were associated with significant metabolic acidemia. In volume-resus citated endotoxemic rats, Pt-O2 and blood pH were unchanged. A significant reduction in the Pt-O2 response to hyperoxia was observed in animals treate d with the NOS inhibitor N-G-nitro-L-arginine methyl ester (L-NAME), an eff ect not reversed by fluid resuscitation. These data suggest that significan t tissue hypoxia and abnormal microvascular control occur in endotoxemia. V olume resuscitation can reverse the changes in Pt-O2, whereas nitric oxide synthase (NOS) inhibition has deleterious effects on muscle Pt-O2 in both c ontrol and endotoxemic animals.